[An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

Tropism of human herpesvirus 8 for peripheral blood lymphocytes in patients with Castleman's disease.

Multicentric Castleman's disease (MCD), also called multicentric angiofollicular lymphoid hyperplasia, is a systemic lymphoproliferative disorder causing fever, lymphadenopathy and splenomegaly. Recently, Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) DNA sequences have been detected in cases of MCD. We examined HHV-8 DNA sequences in the peripheral blood mononuclear cells (PBMCs) of two HIV-negative patients with MCD and in PBMCs and the lymph node of a HIV-negative patient with localized Castleman's disease (LCD) by the polymerase chain reaction. The novel sequences were detected in all DNA samples. Furthermore, the sequences were detected in only the CD19+ B-lymphocyte fraction of the patient with LCD as previously reported. However, the sequences were detected in CD19+ B-lymphocyte and CD2+ T-lymphocyte fractions of two patients with MCD. These results suggest that HHV-8 has tropisms for both B lymphocytes and T lymphocytes in Castleman's disease.

[Acute cardiac failure due to dilated cardiomyopathy in systemic lupus erythematosus with antiphospholipid antibody].

A 33-year-old man presented malar rash in April, 1992. The rash had gradually developed and he was admitted to our hospital in February, 1994. Laboratory findings showed proteinuria of 0.5-0.8 g/ day, thrombocytopenia (4.8 x 10(4)/mm3), false positive serologic test for syphilis, anti-nuclear antibody with a speckled type at a titer of 1 : 80. Activated partial thromboplastin time was prolonged (41.3 s), and anti-beta 2-GPI antibody was strongly positive (56.6 U/ml on enzyme linked immunosorbent assay). The diagnosis of systemic lupus erythematosus with antiphospholipid syndrome was made and prednisolone 60 mg/day improved his manifestations. He could be discharged in July, 1994. Nine months after the discharge he developed dyspnea, and he was admitted to our hospital again. On admission the blood pressure was 212/170 mmHg, Levine III/VI systolic murmur was noted at the apex of heart. Significant laboratory findings showed as follows: WBC 15, 110/mm3 (Neu 73%, Lym 18%), RBC 380 x 10(4)/mm3, Hb 10.2 g/dl, Plt 20.0 x 10(4)/mm3, GOT 23 IU/l, GPT 21.

[A case of Sjögren's syndrome with lymphocytic interstitial pneumonia].

A 73-year-old woman was admitted to our hospital in January 1995 because of dry cough and dyspnea. A diagnosis of primary Sjögren's syndrome with distal renal tubular acidosis and Hashimoto's disease had been made in 1984. Dry cough developed and a chest X-ray showed bilateral reticulo-nodular shadows in the lower lung field in 1992. Her symptoms had gradually became more severe and the reticulo-nodular shadows on her chest X-ray had spread to both upper lung fields. We performed transbronchial lung biopsy. Biopsy specimens showed lymphocytic infiltration of the aleveolar walls. These lymphocytes were almost CD3-positive and CD19-negative in immunohistopathological studies. CD4-positive cells and CD8-positive cells were present in almost equal numbers. A diagnosis of lymphocytic interstitial pneumonia (LIP) associated with Sjögren's syndrome was made. The patient was treated with prednisolone, 40 mg daily. Her dry cough and dyspnea improved slightly but her chest X-ray remained unchanged. We suggest that immunohistopathological analysis of biopsy specimens may show a difference between lymphocytic infiltration of labial salivary glands and of the lung.

[A case of eosinophilic fasciitis with excessive increase of muscle enzyme].

A sixty-year old woman had muscle pain of her extremities and stiffness in her fingers after unusual physical exertion. On admission she developed indurative swellings of the upper extremities and flexion contractures of her fingers. Laboratory data showed peripheral blood eosinophilia and excessive increase of muscle enzymes. Electromyography showed a myopathic pattern and magnetic resonance imaging showed findings of myositis. We performed a full thickness biopsy from skin to muscle. In histopathologic studies, collagenous hypertrophy of the fascia and perifascicular atrophy of muscle fibers and infiltrates on eosinophiles in the interstitial tissue were found. She was treated with prednisolone (60 mg/day). Clinical symptoms showed improvement and her peripheral blood eosinophiles and serum muscle enzymes deminished quickly. In this case, we suggest that the characteristic histopathologic findings in eosinophilic faciitis is not fascia alone, but includes muscle. We stress that eosinophilic faciitis and polymyositis are closely related.

[A case of acute lupus pneumonitis].

Forty-five-year-old woman with systemic lupus erythematosus who had treated with sulindac had exacerbation of her rash and arthralgia. On her admission for treatment, chest X-ray showed bilateral pathy infiltrates in lower lung fields. We performed a transbronchial lung biopsy. Immunohistopathologic studies showed granular deposits of IgM and C 3 in the subendothelial area of pulmonary arteriolae. She was treated with prednisolone (1.0 mg/kg/day) and deoxyspergualin. Chest X-ray showed improvement and her serum IgG, anti-DNA antibodies and complement diminished quickly. We suggest that these immunopathologic observations may be important in the pathogenesis of the lung injury in systemic lupus erythematosus.

[The indications for the use of salazosulfapyridine in rheumatoid arthritis patients].

In an attempt to clarify the background of patients with rheumatoid arthritis (RA) who should be treated with salazosulfapyridine (SASP), a tree classification of responders and non-responders to SASP was developed by analyzing 88 RA patients administered with SASP, according to factors such as clinical findings, autoantibody and HLA antigen. Five clinical features were associated with increased efficacy of SASP: male sex, duration of illness of less than 10 years, initial use of SASP, negative RA test and negative antinuclear antibody. In the tree classification for SASP, there were 3 groups of responders: male sex, female sex + initial use of SASP + negative RA test, and female sex + previous treatment with disease-modifying antirheumatic drugs (DMARDs) +negative antinuclear antibody + negative RA test, while there were 5 groups of non-responders: female sex + previous treatment with DMARDs + negative antinuclear antibody + positive RA test with HLA DR9 or A24 + DR9, and female sex + previous treatment with DMARDs +positive antinuclear antibody with HLA A24, DR9 or A24 + DR9. The new tree classification for the efficacy of SASP in the present study facilitated clear distinction of responders and non-responders to the drug.

A patient with rheumatoid arthritis complicated by Sjögren's syndrome that was possibly caused by reactivation of Epstein-Barr virus.

A 24-year-old woman developed rheumatoid arthritis in 1986. Anti-SS-A antibody was negative, and Sjögren's syndrome was not associated with the disease. In July 1988 the patient developed pyrexia and cervical lymph node swelling. Infectious mononucleosis was suspected, and a previous contact with Epstein-Barr virus (EBV) was indicated. Pyrexia and cervical lymph node swelling occurred repeatedly and after this dry eyes and mouth also developed. In May 1990 the patient again developed pyrexia and cervical lymph node swelling, and she also had anti-SS-A antibodies (64x) and symptoms associated with Sjögren's syndrome. EBV antibody showed reactivation of EBV by the presence of viral capsid antigen-IgM antibody and a decrease in antibody titer against EBV-associated nuclear antigen. The clinical symptoms of repeated fever and cervical lymph node swelling, as well as the reactivation of EBV, suggest that EBV might have been a factor participated in the onset of Sjögren's syndrome in this patient.

[Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report].

We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti-Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sjögren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sjögren's syndrome.

Demonstration of systemic lymphnodes by bone scintigraphy in amyloidosis.

We report a case of primary amyloidosis with calcification of systemic lymphnodes which were demonstrated as positives by bone scintigraphy. Positive sites delineated by bone scintigraphy would seem likely to reflect avid calcification of amyloid deposits. The discovery of positive systemic lymphnodes by bone scintigraphy is very rare in a routine study and may allow for amyloidosis in a differential diagnosis.

[Association of immunomodulators and HLA antigens in rheumatoid arthritis].

We studied the association between HLA antigens and clinical response to immunomodulators or the toxic effects of immunomodulators in 191 patients with rheumatoid arthritis (RA). All patients received nonsteroidal anti-inflammatory drugs. Fifty-seven patients were treated with auranofin, 61 patients with penicillamine and 45 patients with lobenzarit. We found that HLA-Cw 1 is significantly (p less than 0.05) associated with a substantial clinical response to auranofin in RA patients (65% vs 33% of Cw 1-negative patients). We observed that HLA-DR 4 is a risk factor for the occurrence of toxic reactions to penicillamine (45% vs 21% of DR 4-negative patients: p less than 0.05) and that HLA-DRw 9 is a risk factor in the case of lobenzarit (62% vs 32% of DRw 9-negative patients: p less than 0.05). HLA-A 24-positive patients with RA experienced a low frequency of side effects from auranofin (16% vs 37% of A 24-negative patients: p less than 0.05). HLA-A 2 or Cw 7-positive patients with RA experienced a low frequency of side effects from penicillamine (12% vs 49% of A 2-negative patients: p less than 0.01, 17% vs 46% of Cw 7-negative patients: p less than 0.05). Our data demonstrated that HLA antigens are significantly associated with a clinical response to immunomodulators and the toxic effects of immunomodulators in patients with RA.

[Associations of HLA-DR 4, DR 2, DRw 9 with clinical findings in rheumatoid arthritis].

HLA-DR antigens were determined in 128 patients with classical or definite rheumatoid arthritis (RA) according to American Rheumatism Association criteria (1957). HLA-DR 4 was significantly (p less than 0.01) increased in patients with RA (60%) compared with Japanese control (40%). In radiological changes, the frequency of stage II to IV were significantly greater in DR 4 positive patients (87.1% (67/77)) than in negative patients (70.6%) (36/51)). An early onset of disease was significantly (p less than 0.05) associated with DR 4 positive patients with duration of 4 years or more. Erythrocyte sedimentation rate was significantly (p less than 0.05) less in DR 2 positive patients (8.0% +/- 8.6 (39)) than DR 2 negative patients (12.2 +/- 11.9 (84)). Frequency of Sjogren's syndrome was more in DR 2 positive patients (41.3% (12/29)) than in DR 2 negative (29.2% (19/65)), and less in DR 4 positive (25.4% (15/59)) than in DR 4 negative (45.7% (16/35)), so the complication of Sjogren's syndrome showed a trend against the severity of RA. There were no associations between rheumatoid factor and HLA-DR phenotypes, but the frequency of anti-nuclear anti-nuclear antibody was significantly (p less than 0.01) lower in DRw 9 positive patients (38.4% (15/39)) than in DRw 9 negative (62.7% (54/86)). In both DR 4 and DRw 9 positive patients (16 cases), onset of disease (38.9 years-old +/- 15.9 (16)) was significantly earlier and frequency of Sjogren's syndrome (10.0% (1/10)) was significantly lower than those in DR 4 negative patients (48.5 years-old +/- 12.5 (51): 45.7% (15/35) respectively). The frequency of HLA-DRw 9 was greater in Japanese than people in the other countries and there was the close association between pathogenesis of RA and HLA-DRw 9 as well as DR 4 and DR 2 in Japan.